The present invention relates to compositions containing certain hexatriacontapeptides (linear peptides each composed of thirty-six amino acids) which have been recently described as neuropeptides, and more specifically neuropeptide Y (NPY) of porcine or human origin and peptide YY (PYY).
The structure of NPY (porcine), has been established as being: ##STR1## or alternatively, according to the recommendations of the IUPAC-IUB Joint Commission on Nomenclature of amino acids and peptides (Eur. J. Biochem. 1984, 138, 9), with one-letter symbols: ##STR2##
The structure of NPY (human) differs from the above in having Met(M) instead of Leu(L) in position 17.
The structure of PYY is known to be: ##STR3## or, in one-letter symbols: ##STR4##
A variety of pharmacologic activities have been described for NPY and PYY, notably vasoconstrictor effects, natriuretic properties, stimulation of feeding and drinking behaviour, hypertensive effects at high doses and neutrotransmitter or neuromodulator properties.
We have surprisingly found that these peptides, and in particular NPY, when injected into animals at non-pressor doses, almost completely prevent the blood pressure fall induced by endotoxin, such blood pressure fall being frequently lethal to non-treated subjects.
It is a well-known fact, both in animals and in humans, that non-treated hypotension resulting from bacteremic and septic shock, or from anaphylactic, hypovolemic or cardiogenic shock, is frequently fatal.
A common treatment in such cases is the injection or infusion of vasoactive drugs, such as alpha-receptor agonists or antagonists and dopaminergic or beta-receptor stimulants, generally known as inotropic and vasoactive amines.
Such agents however, while counteracting to some extent the hypotensive shock, suffer from the limitation that they affect heart rate which rises frequently to unacceptable levels, requiring th discontinuation of their adminstration. This, in part, explains why presently available therapies have limited efficacy, resulting in a disturbingly high proportion of fatalities. In addition the effect of vasoactive amines is known to wear off with time, thus necessitating repeated administration to obtain the desired results.
The methods of treatment of the present invention improve the therapeutic outcome of such life-threatening conditions, not only because they prevent the severe hypotension which may be fatal, but also because they allow the reduction of doses of vasoactive amines to levels which do not significantly increase the heart rate of the subject.